Abstract
We have previously shown that zinc depletion induces apoptosis in MDA‐MB‐231 cells. Ca2+ is a known mediator of apoptosis. The objective of this study was to establish the role of intracellular Ca2+ in zinc depletion‐induced apoptosis in MDA‐MB‐231 cells. After cultured in DMEM+10% FBS for 3 days, the cells were treated with N,N,N′,N′‐tetrakis[2‐pyridylmethyl]ethylenediamine (TPEN; 20μM) alone for 0–72h or in the presence of 1,2‐bis(2‐ aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid acetoxymethyl ester (BAPTA; 0–40μM) for 6 or 72h. Intracellular Ca2+ was assessed by Fura2 assay. Apoptosis was assessed by caspase‐3 activity and propidium iodide flow cytometric assay. To affirm that TPEN‐induced apoptosis was zinc specific, zinc (0–40μM; 72h) was replenished in the presence of TPEN. TPEN induced a treatment duration‐dependent elevation of intracellular Ca2+ level, caspase‐3 activity, and proportion of apoptotic cells. Zinc replenishment suppressed TPEN‐induced apoptosis. TPEN and BAPTA co‐treatments suppressed TPEN‐induced apoptosis in a dose‐dependent manner. These results suggested that intracellular Ca2+ served as a mediator in zinc depletion‐induced apoptosis in MDA‐MB‐231 cells. Supported by NSERC.
Published Version
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